It is the long-range plan of this project ot study and understand changes in hepatic function following exposure to environmental agents emphasizing effects of hormonally-active chemicals. These studies are defining the liver as a target organ for estrogens by characterizing cytosolic and nuclear estrogen-binding proteins and correlating the presence of receptors with estrogen mediated induction or repression of protein synthesis. The functional biochemical components of estrogen action in adult liver appear to be imprinted during a critical neonatal period by endogenous hormones. The imprinting of sex-dependent hepatic protein synthesis is also evaluated in these studies using a variety of enzyme markers. The pituitary-hypothalamic-hepatic axis appears to regulate the ontogeny of hepatic metabolic competence and the mechanisms involved are investigated in whole animal and culture systems. Alterations in the sex differentiation of hepatic enzymes (specific activities and kinetic constants) are studied in relation to susceptibility to hepatotoxic agents.